1. UNITAID landscape analysis, WHO prequalification of RDTs for HIV-ST, and the role of post-market surveillance Robyn Meurant and Anita Sands WHO Prequalification Team – Diagnostics Assessment 1

2. *With approval from a founding member of the GHTF, All information is provided by manufacturers (UNITAID/WHO Landscape July 2016) HIVST in the informal market is substantially lower US$ 1-11 (in low- and middle-income countries) Assay (Manufacturer)SENSSPECSpecimen Approval Status Price Per Test (US$) Autotest VIH (AAZ Labs, France) 100%99.8% Whole blood CE 25-28 (to consumer) INSTI HIV Self Test (Bioanalytical, Canada) 100%99.8% Whole blood CE 36 (to consumers) Private Sector Version Biosure HIV Self Test (Biosure, UK) 99.7%99.9% Whole blood CE 38-43 (to consumer) Public Sector Version Biosure HIV Self Test (Biosure, UK) 99.7%99.9% Whole blood CE7.50–15 (to public sector) OraQuick In-Home HIV Test (OraSure Technologies, USA) 100%99.8%Oral Fluid Pendin g CE NA OraQuick In-Home HIV Test (OraSure Technologies, USA) 91.7%99.9%Oral FluidFDA40 (to consumer) RDTs for HIV ST on the market

3. Assay (Manufacturer)SENSSPECSpecimenApproval Status Price Per Test (US$) Atomo HIV Self-Test (AtomoDiagnostics, Australia) NA Whole bloodNo infoNA Exacto HIV Screening Test (Biosynex Medtech, France) NA Whole blood Submitting dossier for CE mark NA HemaDiagnostics Self-Test (Hema Diagnsotics Systems LLC; USA) NA Whole bloodNo infoNA To be named (Chembio Diagnostics Systems Inc. USA) NA Whole blood No infoNA To be named (Alere, USA) NA Whole bloodNo infoNA To be named (Trinity Biotech Manufacturing Ltd, Ireland) NA Whole bloodNo infoNA To be named (Sedia Biosciences, USA) NA Oral fluidNo infoNA Aware™ HIV-1/2 OMT Oral HIV ST (Calypte Biomedical Corporation, USA) NA Oral fluidNo infoNA HIV Self-Test (OraSure Technologies, Bangkok, Thailand) NA Oral fluidNo infoNA *All information is provided by manufacturers (UNITAID/WHO Landscape July 2016) Pipeline of RDTs for HIV ST

4. Role of WHO Essential Medicines & Health Products Promote and facilitate access to safe, reliable and appropriate in vitro diagnostics in an equitable manner through:  Prequalification of in vitro diagnostics and post- market surveillance;  Capacity building of national regulatory authorities and national reference laboratories;  Facilitating procurement of affordable and appropriate IVDs  Facilitating quality assurance programmes;  Providing policy, guidance and advocacy to Member States.

5. What is a testing purpose? Why is it important? Test purposes: diagnosis, aid to diagnosis, screening, monitoring, etc.  RDTs for self-testing don't have the same testing purpose as RDTs for professional use The testing purpose is critical  For manufacturer to validate/verify their product appropriately for the intended use  For regulators and WHO to determine when a product is acceptable for a given intended use

6. Pre-submission form Dossier review Site inspection Performance evaluation Dossier incomplete PREQUALIFICATION DECISION Dossier complete Dossier screening Priority product Yes No Post - Qualification activities (change notification, PMS, EQA, support…) WHO Prequalification Procedure

7. Performance specifications: HIV RDTs for ST Principles:  Requires sound analytical and clinical performance characteristics, as for professional use RDTs  Performance must reflect intended users and their setting  Subtypes, interfering factors, stability  WHO PQ requirements address clinical validity:  Clinical validity (e.g. device can detect HIV-1/2 antibodies and be used in diagnosis) vs clinical utility (e.g. effectiveness of self diagnosis as an intervention)

8. Change notification form Documentation review PREQUALIFICATION DECISION Post - Qualification activities (change notification, PMS, EQA, support…) Scenario 1: PQed for professional use, adding ST claim Supportive evidence submitted for ST claim PQ change notification

9. Post - Qualification activities (change notification, PMS, EQA, support…) Scenario 2a: Professional use PQ in progress, adding claim for ST Pre-submission form Dossier review Site inspection Performance evaluation Dossier incomplete PREQUALIFICATION DECISION Dossier complete Dossier screening Priority product Yes No Review supportive evidence for ST

10. Pre-submission form Abbreviated site inspection Performance evaluation Priority product Yes No Post - Qualification activities (changes, PMS, EQA, support…) Abbreviated PQ Procedure PREQUALIFICATION DECISION

11. Scenario 2b: Abbreviated PQ in progress, adding claim for ST Pre-submission form Site inspection Performance evaluation Priority product Yes No ST Claim Full dossier requested ST Claim Full dossier requested Dossier review Post - Qualification activities (change notification, PMS, EQA, support…) PREQUALIFICATION DECISION

12. Post - Qualification activities (change notification, PMS, EQA, support…) Scenario 3: New IVD, Manufacturer known to PQ Pre-submission form Dossier review Site inspection Performance evaluation Dossier incomplete PREQUALIFICATION DECISION Dossier complete Dossier screening Priority product Yes No

13. Post - Qualification activities (change notification, PMS, EQA, support…) Scenario 3: New IVD, Manufacturer known to PQ Pre-submission form Dossier review Site inspection Performance evaluation Dossier incomplete PREQUALIFICATION DECISION Dossier complete Dossier screening Priority product Yes No

14. Post - Qualification activities (change notification, PMS, EQA, support…) Scenario 4: New IVD, New Manufacturer Pre-submission form Dossier review Site inspection Performance evaluation Dossier incomplete PREQUALIFICATION DECISION Dossier complete Dossier screening Priority product Yes No

15. Product nameIntended use Autotest VIHSubmitted for self-testing use Current WHO PQ pipeline for HIV RDTs for ST

16. Performance specifications: HIV RDTs (for ST) WHO PQ is developing guidance documents to assist manufacturers  Technical guidance series (TGS-1, etc.)  Sample dossiers (e.g. HIV RDT for ST)  "Technical Specifications" series (TSS) with minimum testing requirements http://www.who.int/diagnostics_laboratory/guidance/en/

17. What happens after WHO PQ Manufacturer has specific obligations to maintain PQ:  Conduct post-market surveillance - such as complaint reporting (including adverse events)  Notify to WHO of any changes to the product or the quality management system at the manufacturing site  Annual reporting of complaints and sales data to determine when WHO will re-inspect

18. Incident is something that happens to the IVD e.g. stored outside of recommended storage conditions, reading time wasn't observed Adverse event is something that happens to a person e.g. death or serious deterioration in health, false negative, false positive result where it leads to a misdiagnosis Post-market surveillance is necessary to detect, investigate and act on any issues that compromise individual health or public health related to use of an IVD Incident vs. adverse event

19. WHO post-market surveillance of IVDs

20. Reporting complaints (incidents and adverse events) to manufacturer  Insufficient buffer to complete test;  Excessively high background;  Test strip is misplaced  Visually obvious migration issues;  Dry alcohol swabs;  Very soft or very stiff specimen transfer devices  False negative/false positive results Following the instructions of any safety notice that indicates a corrective action should be taken  E.g. lot recall, modification of test procedure (IFU), etc. Reactive PMS Possible issuance of Field Safety Notice Complaint Possible Field Safety Corrective Action The role of the self-tester in PMS Take a photo - ensure product name & lot number can be seen

21. Roles and responsibilities of stakeholders Template forms  IVD complaint form  Manufacturer complaint investigation report  Field Safety Corrective Action report  Lot testing data collection & report Template notices  Field Safety Notice WHO reserves the right to issue a WHO Information Notice for Users WHO normative guidance for PMS of IVDs

22. Contact us By email diagnostics@who.int Sign up to our mailing list By emailing diagnostics@who.int Via our website http://www.who.int/diagnostics_laboratory /en/ http://www.who.int/diagnostics_laboratory /postmarket/en/